The impact of invisible-spreaders on COVID-19 transmission and work resumption

The global impact of coronavirus disease 2019 (COVID-19) is unprecedented, and many control and prevention measures have been implemented to test for and trace COVID-19. However, invisible-spreaders, who are associated with nucleic acid detection and asymptomatic infections, have received insufficient attention in the current COVID-19 control efforts. In this paper, we analyze the time series infection data for Italy, Germany, Brazil, India and Sweden since the first wave outbreak to address the following issues through a series of experiments. We conclude that: 1) As of June 1, 2020, the proportion of invisible-spreaders is close to 0.4% in Sweden, 0.8% in early Italy and Germany, and 0.4% in the middle and late stages. However, in Brazil and India, the proportion still shows a gradual upward trend; 2) During the spread of this pandemic, even a slight increase in the proportion of invisible-spreaders could have large implications for the health of the community; and 3) On resuming work, the pandemic intervention measures will be relaxed, and invisible-spreaders will cause a new round of outbreaks.

Asymptomatic and Submicroscopic Plasmodium Infections in an Area Before and During Integrated Vector Control in Homa Bay, Western Kenya

Background Long lasting insecticidal bednets (LLINs) have been the primary vector control strategy until indoor residual spraying (IRS) was added in Homa Bay and Migori Counties in western Kenya. The objective of this study was to evaluate the impact of LLINs integrated with organophosphate-based (Actellic 300 CS) IRS on the prevalence of asymptomatic and submicroscopic Plasmodium species infections in Homa Bay County. Methods Four consecutive community cross-sectional surveys for Plasmodium species infection were conducted in residents of Homa Bay County, Kenya commencing immediately before and 2 years after introduction of annual IRS. Finger-prick blood samples were obtained to prepare thick and thin smears for microscopic determination and qPCR diagnosis of Plasmodium genus, P. falciparum, P. malariae and P. ovale infection. Results Plasmodium spp. infection prevalence by microscopy was 18.5% before IRS and 14.2%, 3.3% and 1.3% after two annual rounds of IRS (χ²= 186.9, df = 3, p < 0.0001). Submicroscopic (blood smear negative, qPCR positive) parasitemia was 50.4% before IRS and 43.2%, 68.0% and 80.7% after IRS (χ²= 31.98, df = 3, p < 0.0001). Geometric mean density of P. falciparum parasitemia decreased over the 2-year study period (ANOVA, F = 28.95, df = 3, 243, p < 0.0001). The proportion of blood smear positive asymptomatic infections that included P. falciparum did not significantly change over the study period. In contrast, the proportion of asymptomatic submicroscopic P. falciparum infections trended upward following introduction of IRS (pre-IRS 48.2% versus post-IRS 41.6%, 61.3% and 75.4%; (χ²= 24.00, df = 3, p = 0.0002). Conclusions These data suggest that two annual rounds of IRS integrated with LLIN significantly reduced the prevalence of Plasmodium parasitemia, whereas the proportion of submicroscopic infections that included P. falciparum parasite increases. Strategies that aim at reducing the number of asymptomatic submicroscopic infections should be considered to diminish cryptic P. falciparum transmission and enhance malaria control.

Estimating the Proportion of Asymptomatic COVID-19 Cases in an Italian Region with Intermediate Incidence during the First Pandemic Wave: An Observational Retrospective Study

Early in the COVID-19 pandemic, asymptomatic transmission represented an important challenge for controlling the spread of SARS-CoV-2 through the traditional public health strategies. Further understanding of the contribution of asymptomatic infections to SARS-CoV-2 transmission has been of crucial importance for pandemic control. We conducted a retrospective epidemiological study to characterize asymptomatic COVID-19 cases occurred in the Apulia region, Italy, during the first epidemic wave of COVID-19 outbreak (February 29-July 7, 2020). We analyzed data collected in a regional platform developed to manage surveillance activities, namely, investigation and follow-up of cases and contacts, contact tracing, and laboratory and clinical data collection. We included all asymptomatic cases that were laboratory-confirmed during the appropriate follow-up, defined as persons infected with SARS-CoV-2 who did not develop symptoms/clinical signs of the disease. Between February 29 and July 7, 2020, a total of 4,536 cases were diagnosed with COVID-19 among 193,757 tests performed. The group of persons with asymptomatic SARS-CoV-2 infection consisted of 903 cases; the asymptomatic proportion was 19.9% (95% CI: 18.8-21.1%); this decreased with increasing age (OR: 0.89, 95% CI: 0.83-0.96; p = 0.001 ), in individuals with underlying comorbidities (OR: 0.55, 95% CI: 0.41-0.73; p < 0.001 ), and in males (OR: 0.69, 95% CI: 0.54-0.87; p = 0.002 ). The median asymptomatic SARS-CoV-2 RNA positive period was 19 days (IQR: 14-31) and the cumulative proportion of persons with resolution of infection 14 days after the first positive PCR test was 74%. As the public health community is debating the question of whether asymptomatic and late spreaders could sustain virus transmission in the communities, such cases present unique opportunities to gain insight into SARS-CoV-2 adaptation to human host. This has important implications for future COVID-19 surveillance and prevention.

Identification of asymptomatic Leishmania infections: a scoping review

Background Asymptomatic Leishmania infection may play an important role in the transmission of the parasite in endemic areas. At present there is no consensus on the definition of asymptomatic Leishmania infection, nor is there a safe and accessible gold standard test for its identification. Methods This paper presents a scoping review to summarize definitions of asymptomatic Leishmania infection found in the literature, as well as to detail the approach (molecular, serological, cellular, and/or parasitological tests) used by researchers to identify this asymptomatic population. A scoping review of published and gray literature related to asymptomatic Leishmania infection was conducted; retrieved citations were screened based on predefined eligibility criteria, and relevant data items were extracted from eligible articles. The analysis is descriptive and is presented using tables, figures, and thematic narrative synthesis. Results We conducted a screening of 3008 articles, of which 175 were selected for the full review. Of these articles, we selected 106 that met the inclusion criteria. These articles were published between 1991 and 2021, and in the last 5 years, up to 38 articles were reported. Most of the studies were conducted in Brazil (26%), Spain (14%), India (12%), Bangladesh (10%), and Ethiopia (7%). Of the studies, 84.9% were conducted in the immunocompetent population, while 15.1% were conducted in the immunosuppressed population (HIV, immunosuppressive drugs, and organ transplantation population). We report 14 different techniques and 10 strategies employed by researchers to define asymptomatic Leishmania infection in an endemic area. Conclusions The definition of asymptomatic Leishmania infection is not unified across the literature, but often includes the following criteria: residence (or extended stay) in a Leishmania-endemic area, no reported signs/symptoms compatible with leishmaniasis, and positive on a combination of serological, molecular, cellular, and/or parasitological tests. Caution is recommended when comparing results of different studies on the subject of asymptomatic infections, as the reported prevalence cannot be confidently compared between areas due to the wide variety of tests employed by research groups. More research on the importance of asymptomatic immunosuppressed and immunocompetent Leishmania-positive populations in leishmaniasis epidemiology is required. Graphical Abstract

Rapid Antigen Test Combine with Nucleic Acid Detection: A Better Strategy for COVID-19 Screening at Points of Entry

The coronavirus disease 2019 (COVID-19) pandemic has imposed an enormous disease burden worldwide, and the Delta variant now has become dominant in 53 countries. Recently published studies have shown that during periods of high viral load, rapid antigen tests (RAT) yield similar results to reverse transcriptase-polymerase chain reaction (RT-PCR) tests, and when used in serial screening (e.g., every three days), it has a high sensitivity. In this perspective, we recommend RT-PCR combined with RAT at points of entry: (i) RAT can be added to the detection phase at ports of entry to detect asymptomatic infections as early as possible; (ii) RAT can be added to post-entry quarantine every three days or less to reduce the rate of missed detection in later quarantine; (iii) Adding regular RAT to regular PCR testing for key airport personnel to prevent cross-infection and conduct closed-off management. In the face of sporadic Delta variant outbreaks, the combination of the two could help rapid triage and management of suspected populations at an early stage and thus contain the outbreak more quickly and effectively. We also discuss the issue whether the current antigen detection reagents can cope with various SARS-CoV-2 variants.

First Detection of Rotavirus C in Asymptomatic Pigs from India with Unexpected Dominance and Characterization of the Structural and Nonstructural Genes

Epidemiological and molecular investigation was conducted on Rotavirus C (RVC), the viral agent documented with rising prevalence rate, disease severity and cross species transmission and large outbreak potential. Fecal specimens of pigs collected from two cities of Maharashtra state, India tested for RVC showed 20.1% detection rate with majority below 3 months of age. No significant difference in detection rates was observed in the specimens collected in 2009 from Northern and in 2013 from Western parts of Maharashtra. The phylogenetic analyses showed presence of the I7 and I10 genotypes of the VP6 gene and representative strains with G1 and E5 genotypes of the VP7 and NSP4 gene respectively. Full genome characterization of a single strain showed presence of G1, P1, I7, R1, C1, M3, A1, N5, T5, E5, H1 genotypes of the VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5 genes respectively. This is the first evidence of detection of porcine RVC in asymptomatic pigs in India as well as with highest detection rate reported in asymptomatic pigs till date globally. Identification of porcine RVC at two time intervals and two different parts of Maharashtra state indicates the possibility of continuous circulation of RVC in pig population through asymptomatic infections.

Estimating the proportion of asymptomatic COVID-19 cases in an Italian region with intermediate incidence during the first pandemic wave: an observational retrospective study

Early in the COVID-19 pandemic, asymptomatic transmission represented an important challenge for controlling the spread of SARS-CoV-2 through the traditional public health strategies. Further understanding of the contribution of asymptomatic infections to SARS-CoV-2 transmission has been of crucial importance for pandemic control. We conducted a retrospective epidemiological study to characterize asymptomatic COVID-19 cases occurred in the Apulia region, Italy, during the first epidemic wave of COVID-19 outbreak (February 29 - July 7, 2020). We analyzed data collected in a regional platform developed to manage surveillance activities, namely investigation and follow-up of cases and contacts, contact tracing, laboratory and clinical data collection. We included all asymptomatic cases that were laboratory-confirmed during the appropriate follow-up, defined as persons infected with SARS-CoV-2 who did not develop symptoms/clinical signs of the disease. Between February 29 and July 7, 2020, a total of 4,536 cases were diagnosed with COVID-19 among 193,757 tests performed. The group of persons with asymptomatic SARS-CoV-2 infection consisted of 903 cases; the asymptomatic proportion was 19.9% (95%CI: 18.8-21.1%); this decreased with increasing age (OR: 0.89, 95%CI: 0.83-0.96; p=0.001), in individuals with underlying comorbidities (OR: 0.55, 95%CI: 0.41-0.73; p<0.001), and in males (OR: 0.69, 95%CI: 0.54-0.87; p=0.002). The median asymptomatic SARS-CoV-2 RNA positive period was 19 days (IQR: 14-31) and the cumulative proportion of persons with resolution of infection 14 days after the first positive PCR test was 74%. As the public health community is debating the question of whether asymptomatic and late spreaders could sustain virus transmission in the communities, such cases present unique opportunities to gain insight into SARS-CoV-2 adaptation to human host. This has important implications for future COVID-19 surveillance and prevention.

Human serum from SARS-CoV-2 vaccinated and COVID-19 patients shows reduced binding to the RBD of SARS-CoV-2 Omicron variant in comparison to the original Wuhan strain and the Beta and Delta variants

Background The ongoing COVID-19 pandemic is caused by the beta coronavirus SARS-CoV-2. COVID-19 manifests itself from mild or even asymptomatic infections to severe forms of life-threatening pneumonia. At the end of November 2021, yet another novel SARS-CoV-2 variant named B.1.1.529 or Omicron was discovered and classified as a variant of concern (VoC) by the WHO. Omicron shows significantly more mutations in the amino acid (aa) sequence of its spike protein than any previous variant, with the majority of those concentrated in the receptor binding domain (RBD). In this work, the binding of the Omicron RBD to the human ACE2 receptor was experimentally analyzed in comparison to the original Wuhan SARS-CoV-2 virus, and the Beta and Delta variants. Moreover, we compared the ability of human sera from COVID-19 convalescent donors and persons fully vaccinated with BNT162b2 (Corminaty) or Ad26.COV2.S (Janssen COVID-19 vaccine) as well as individuals who had boost vaccine doses with BNT162b2 or mRNA-1273 (Spikevax) to bind the different RBDs variants. Methods The Omicron RBD with 15 aa mutations compared to the original Wuhan strain was produced baculovirus-free in insect cells. Binding of the produced Omicron RBD to hACE was analyzed by ELISA. Sera from 27 COVID-19 patients, of whom 21 were fully vaccinated and 16 booster recipients were titrated on the original Wuhan strain, Beta, Delta and Omicron RBD and compared to the first WHO International Standard for anti-SARS-CoV-2 immunoglobulin (human) using the original Wuhan strain as reference. Results The Omicron RBD showed a slightly reduced binding to ACE2 compared to the other RBDs. The serum of COVID-19 patients, BNT162b2 vaccinated and boost vaccinated persons showed a reduced binding to Omicron RBD in comparison to the original Wuhan strain, Beta und Delta RBDs. In this assay, the boost vaccination did not improve the RBD binding when compared to the BNT162b2 fully vaccinated group. The RBD binding of the Ad26.COV2.S serum group was lower at all compared to the other groups. Conclusions The reduced binding of human sera to Omicron RBD provides first hints that the current vaccinations using BNT162b2, mRNA-1273 and Ad26.COV2.S may be less efficient in preventing infections with the Omicron variant.